Synthesis of (Bromo-η ⁴-2-pyrone)tricarbonyliron Complexes

Abstract

The addition of the tricarbonyliron ‘Fe(CO)₃’ unit to several bromo-substituted 2-pyrones has been investigated. Direct reaction with Fe₂(CO)₉ in benzene at 80 ºC results in poor yields and hydrodebromination. Switching the solvent to n-Bu₂O, sequential addition of Fe₂(CO)₉ and slow passage of N₂ through the solution improves the yields of the tricarbonyliron complexed 2-pyrones. Direct ‘Fe(CO)₃’ transfer reagents such as (η ⁴-benzylidene­acetone)tricarbonyliron or generic (η ⁴-1-azabuta-1,3-diene)tricarbonyliron complexes, under both stoichiometric and catalytic conditions, fails to give the desired complexes. Surprisingly, the unstable bis(η ²-cis-cyclooctene)Fe(CO)₃ (Grevels’ reagent) did serve as a useful transfer reagent.

Key words

2-pyrones - tricarbonyliron - hydrodebromination - Grevels’ reagent

References

• 1a Dickinson JM. Nat. Prod. Rep.  1993,  10:  71 
• 1b Vardaro RR. DiMarzo V. Crispino A. Cimino G. Tetrahedron  1991,  47:  5569 
• 1c Groutas WC. Stanga MA. Brubaker MJ. Huang TL. Moi MK. Carroll RT. J. Med. Chem.  1985,  28:  1106 
• 2a Lee J.-H. Kim W.-S. Lee YY. Cho C.-G. Tetrahedron Lett.  2002,  43:  5779 
• 2b Lee J.-H. Park J.-S. Cho C.-G. Org. Lett.  2002,  4:  1171 
• 3a Shi X. Leal WS. Liu Z. Schrader E. Meinwald J. Tetrahedron Lett.  1995,  36:  71 
• 3b Leal WS. Shi X. Liang D. Schal C. Meinwald J. Proc. Natl. Acad. Sci. U.S.A.   1995,  92:  1033 
• 4 Cerezo S. Moreno-Mañas M. Pleixats R. Tetrahedron  1998,  54:  7813 
• 5a Marrison LR. Dickinson JM. Fairlamb IJS. Bioorg. Med. Chem. Lett.  2002,  12:  3509 
• 5b Marrison LR. Dickinson JM. Ahmed R. Fairlamb IJS. Tetrahedron Lett.  2002,  43:  8853 
• 5c Marrison LR. Dickinson JM. Ahmed R. Fairlamb IJS. Bioorg. Med. Chem. Lett.  2003,  13:  2667 
• 6 Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1997. 
• 7 Semmelhack MF. Tamura R. Schnatter W. Springer J. J. Am. Chem. Soc.  1984,  106:  5363 
• 8 Mitsudo T. Watanabe Y. Nakanishi H. Morishima I. Inubushi T. Takegami Y. J. Chem. Soc., Dalton Trans.  1978,  1298 
• 9 Mitsudo T. Watanabe H. Sasaki T. Takegami Y. Watanabe Y. Kafuku K. Nakatsu K. Organometallics  1989,  8:  368 
• 10 Mitsudo T.-A. Watanabe H. Sasaki T. Watanabe Y. Takegami Y. Kafuku K. Kinoshita K. Nakatsu K. J. Chem. Soc., Chem. Commun.  1981,  22 
• 11 DePuy CH. Parton RL. Jones T. J. Am. Chem. Soc.  1977,  99:  4070 
• 12 Rosenblum M. Gatsonis C. J. Am. Chem. Soc.  1967,  89:  5074 
• 13 Seyferth D. Organometallics  2003,  22:  2 
• 14 Cervera M. Moreno-Mañas M. Pleixats R. Tetrahedron  1990,  46:  7885 
• 15a Reduction of 1,2,5,6-tetrabromopyracene by Fe₂(CO)₉ to produce pyracylene has been reported (in diethyl ether, 25 ºC), see: Trost BM. Bright GM. J. Am. Chem. Soc.  1969,  91:  3689 
• 15b For further reductions of Csp³-X bonds by Fe₂(CO)₉, see: Efraty A. Chem. Rev.  1977,  77:  691 
• 16 Brune HA. Horlbeck G. Zhorszky UIZ. Z. Naturforsch., B: Chem. Sci.  1971,  26:  222 
• 17a Banwell MG. Schuhbauer HM. Organometallics  1996,  15:  4078 
• 17b

  The dehalogenated tricarbonyliron complexes of 3-bromo and 4-bromo-tropone (2,4,6-cycloheptatrien-1-one) were not detected by Banwell’s group, private communication (2003).

• 18a Harrity JPA. Kerr WJ. Middlemiss D. Tetrahedron Lett.  1993,  34:  2995 
• 18b Harrity JPA. Kerr WJ. Midlemiss D. Tetrahedron  1993,  49:  5565 
• 18c Harrity JPA. Kerr WJ. Middlemiss D. Scott JS. J. Organomet. Chem.  1997,  532:  219 
• 18d Caldwell JJ. Colman R. Kerr WJ. Magennis EJ. Synlett  2001,  1428 
• 19 Knölker H.-J. Chem. Soc. Rev.  1999,  28:  151 ; and references cited therein
• 20a Sugihara T. Yamada M. Yamaguchi M. Nishizawa M. Synlett  1999,  771 
• 20b Kerr WJ. Lindsay DM. McLaughlin M. Pauson PL. Chem. Commun.  2000,  1467 
• 22 Knölker H.-J. Baum E. Foitzik H. Goesmann P. Gonser P. Jones G. Röttele H. Eur. J. Inorg. Chem.  1998,  993 ; and references cited therein
• 23 Fleckner H. Grevels F.-W. Hess D. J. Am. Chem. Soc.  1984,  106:  2027 
• 24a Knölker H.-J. Gonsor P. Synlett  1992,  517 
• 24b Knölker H.-J. Gonsor P. Jones PG. Synlett  1994,  405 
• 25 Alcock NW. Richards CJ. Thomas SE. Organometallics  1991,  10:  231 
• 26 Knölker H.-J. Baum E. Gonser P. Rohde G. Röttele H. Organometallics  1998,  17:  3916 
• 27 Ley SV. Cox LR. Meek G. Chem. Rev.  1996,  96:  423 
• 29 Compounds 21a and 21b gave satisfactory characterisation data (IR, ¹H, ¹³C NMR, LRCI and HRCI). Compound 21a was accompanied by a side-product: (η ⁴-4-(4′-methoxy-phenyl)-6-methyl-2-pyrone)Fe(CO)₂PPh₃. The ³¹P NMR signal (δ 72.51) is similar to that reported for (η ⁴-1,3-cyclohexadiene)Fe(CO)₂PPh₃ (δ 70.2), see: Howell JAS. Walton G. Tirvengadum M.-C. Squibb AD. Palin MG. McArdle P. Cunningham D. Goldschmidt Z. Gottlieb H. Strul G. J. Organomet. Chem.  1991,  401:  91 

21

General procedure for complexation studies with Fe₂(CO)₉: Caution: Fe(CO) ₅ and Fe ₂ (CO) ₉ are highly toxic; Fe(CO) ₅ is volatile. To a dried Schlenk tube under N₂ were added Fe₂(CO)₉ (0.5 equiv) and the recrystallised 2-pyrone (1 equiv). Degassed anhydrous n-Bu₂O (10-12 mL per mmol) was added via cannula and the mixture stirred at 65 ºC for 0.5 h whilst N₂ was bubbled through slowly. Two further portions of Fe₂(CO)₉ (0.5 equiv) were added at 0.5 h intervals. After 2 h, the mixture was allowed to cool to r.t. and the solvent removed in vacuo. Purification by column chromatography using petroleum ether (40-60 ºC)/ethyl acetate (9:1), which was increased to 3:1 after 10 fractions, gave the expected brominated pyrone complex, followed by starting material and then the hydrodebrominated 2-pyrone Fe(CO)₃ complex. Note: On several occasions we have also isolated Fe₃(CO)₁₂ (dark green) in small quantities from the reactions (elutes first).
( η ⁴ -4-Bromo-6-methyl-2-pyrone)tricarbonyl iron (11).
R_f = 0.45 (petroleum ether 40-60 ºC/ethyl acetate, 3:1). Mp 106-107 ºC (decomp.), dark orange solid. IR (CH₂Cl₂) 2075, 2010, 1743, 1604. δ_H (400 MHz, CDCl₃) 1.88 (3 H, s, CH ₃ ), 3.38 (1 H, s, H3), 5.84 (1 H, s, H5). δ_C (100 MHz, CDCl₃) 22.37 (CH₃), 54.42 (C3), 81.34 (C5), 93.72 (C4), 98.59 (C6), 168.39 (C2), 206.32 (br, 3 × CO). LRCI m/z 346/348 (M + NH₄Br⁷⁹/Br⁷⁸, 33%), 329/331 (MH⁺ Br⁷⁹/Br⁸¹, 18%), 236, 219, 189/191 [M - Fe(CO)₃] 128, 111 (M - Fe(CO)₃ - Br, 100%). HRCI m/z exact mass calculated for C₉H₅O₅BrFe 328.8747; Found, 328.8745. ( η ⁴ -6-Methyl-2-pyrone)tricarbonyliron (12). R_f = 0.22 (petroleum ether 40-60 ºC/ethyl acetate, 3:1). Mp 94-95 ºC (decomp.), orange solid. IR (CH₂Cl₂) 2065, 1999, 1739, 1604 cm^-1. δ_H (400 MHz, CDCl₃) 1.91 (3 H, s, CH ₃ ), 2.94
(1 H, d, ³ J _HH = 5.9 Hz, H3), 5.45 (1 H, d, ³ J _HH = 3.3 Hz, H5), 6.15 (1 H, dd, ³ J _HH = 5.9 Hz, 3.3 Hz, H4). δ_C (100 MHz, CDCl₃) 22.63 (CH₃), 48.61 (C3), 76.41 (C5), 86.84 (C4), 104.19 (C6), 170.10 (C2), 207.62 (br, 3 × CO). LRCI m/z 268 (M + NH₄, 97%), 251 (MH⁺, 100%), 128, 111 [M - Fe(CO)₃, 48%]. HRCI m/z exact mass calculated for C₉H₆O₅Fe 250.9642; Found, 250.9639.
( η ⁴ -5-Bromo-2-pyrone)tricarbonyliron (15). R_f = 0.44 (petroleum ether 40-60 ºC/ethyl acetate, 3:1). Mp 73-75 ºC (decomp.), yellow solid. IR (CH₂Cl₂) 2066, 2002, 1740, 1604. δ_H (400 MHz, CDCl₃) 2.95 (1 H, d, ³ J _HH = 6.3 Hz, H3), 5.68 (1H, d, ⁴ J _HH = 2.6 Hz, H6), 6.47 (1 H, dd, ³ J _HH = 6.3 Hz, ⁴ J _HH = 2.6 HZ, H4). δ_C (100 MHz, CDCl₃) 45.47 (C3), 84.30 (C5), 90.40 (C6), 93.19 (C4), 159.44 (C2), 205.85 (br, 3 × CO). LRCI m/z 332/334 (M + NH₄ Br⁷⁹/Br⁸¹, 100%), 315/317 (MH⁺ Br⁷⁹/Br⁸¹, 45%), 247/249 (Br⁷⁹/Br⁸¹), 114, 97 [M - Fe(CO)₃ - Br], 90. HRCI m/z exact mass calculated for C₈H₃O₅BrFe 314.8591; Found, 314.8586.

28

The crystal structures of 11 and 12 have been deposited to the Cambridge Crystallographic Database (UK). Deposit numbers are CCDC 210379 and CCDC 210380, respectively.
Crystal data for 11. C₉H₅O₅BrFe, M = 328.89, triclinic, a = 6.562 (2), b = 7.091 (2), c = 12.565 (4) Å, U = 529.7 (3) ų _, T = 113 (2) K, space group P-1, Z = 2, µ(Mo-K_a) = 1.546 mm^-1, reflections measured 2902, unique 1858 (R _int = 0.0386) which were used in all calculations. The final wR(F ²) was 0.0992 (all data).
Crystal data for 12. C₉H₆O₅Fe, M = 249.99, triclinic, a = 6.3565 (6), b = 7.5012 (7), c = 10.2161 (10) Å, U = 486.34 (8) ų _, T = 113 (2) K, space group P-1, Z = 2, µ(Mo-K_a) = 1.546 mm^-1, reflections measured 3864, unique 2702 (R _int = 0.0135) which were used in all calculations. The final wR(F ²) was 0.0760 (all data).